Clinical Trial Results:
CHECKPOINT INHIBITOR INDUCED COLITIS AND ARTHRITIS –
IMMUNOMODULATION WITH IL-6 BLOCKADE AND
EXPLORATION OF DISEASE MECHANISMS
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Summary
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EudraCT number |
2018-002595-41 |
Trial protocol |
DK |
Global end of trial date |
29 Sep 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
10 Oct 2021
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First version publication date |
10 Oct 2021
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
AA1820
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03601611 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Herlev and Gentofte Hospital, Department of Oncology
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Sponsor organisation address |
Borgmester Ib Juuls Vej 1, Herlev, Denmark, 2730
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Public contact |
Coordinating Investigator, Herlev and Gentofte Hospital, +45 38682898, inna.chen@regionh.dk
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Scientific contact |
Coordinating Investigator, Herlev and Gentofte Hospital, +45 38682898, inna.chen@regionh.dk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
29 Sep 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
29 Sep 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
29 Sep 2020
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the clinical benefit of IL-6 inhibition by tocilizumab on diarrhea and/or colitis and/or arthritis induced by checkpoint inhibitors in patients with solid tumors within 8 weeks of treatment start.
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Protection of trial subjects |
Patients that signed informed consent and fulfilling eligibility criteria were included. Continued monitoring of standard safety parameters during treatment.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
24 Jan 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Denmark: 20
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Worldwide total number of subjects |
20
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EEA total number of subjects |
20
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
10
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From 65 to 84 years |
10
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85 years and over |
0
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Recruitment
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Recruitment details |
The trial was opened for recruitment in January 2019 and closed for enrollment in January 2020 per protocol. Patients were included at a single site, Herlev Hospital, Denmark. | ||||||||||
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Pre-assignment
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Screening details |
Eligible patients were 18 years or older with solid tumors who were treated with ICIs and had grade >1 ir-colitis and/or ir-arthritis . Systemic glucocorticoids or other immunosuppressive drugs were not allowed within a 14-day screening period. | ||||||||||
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Period 1
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Period 1 title |
Treatment (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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Tocilizumab | ||||||||||
Arm description |
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Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Tocilizumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Patients will receive tocilizumab 8 mg/kg milligram(s)/kilogram, Q4W for at least 2 cycles or until worsening or lack of improvement of symptoms, in case of unacceptable toxicity, withdrawal of consent or clear clinical deterioration
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Baseline characteristics reporting groups
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Reporting group title |
Treatment
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
efficacy
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Subject analysis set type |
Per protocol | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Patients with confirmed diagnosis of ir-arthritis , ir-colitis or both, that have recieving at least one dose of tocilizumab.
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End points reporting groups
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Reporting group title |
Tocilizumab
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Reporting group description |
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Subject analysis set title |
efficacy
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Patients with confirmed diagnosis of ir-arthritis , ir-colitis or both, that have recieving at least one dose of tocilizumab.
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End point title |
≥1 grade improvement at week 8 [1] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
8 weeks after treatment start.
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: According to Simon’s 2-stage optimal design, a sample size of 20 is required to be able to confirm the alternative hypothesis that symptom improvement in ≥ 80% of patients with 80% probability given the alternative hypothesis is true and reject the null hypothesis that symptom improvement is < 50% with 5% probability given that the null hypothesis is true. The alternative hypothesis will be rejected if at least one grade improvement is observed for ≤13 patients. |
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| Notes [2] - For 1 of the 20 patients irColitis was not confirmed and patient was excluded from efficacy analysis |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
sustained glucocorticoid-free remission at week 24 | ||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
24 weeks after treatment start
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Adverse events information
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Timeframe for reporting adverse events |
From start of treatment until 30 days after last dose
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Adverse event reporting additional description |
All serious AE are reported. non serious event with relationship to tocilizumab only
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
NCI-CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
5
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Reporting groups
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Reporting group title |
Tocilizumab
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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31 Jan 2019 |
amended to enhance clarity and consistency of the protocol. Additionally, study times lines were updated
- clarify specific blood tests, separating rheumatological and gastrointestinal analyses respectively and analyses for all patients.
- Timepoint clarification of fecal specimens collection
- Clarification of definition of EOT and EOS visit in case of treatment duration of ≥6 months.
- Clarification of days and study assessment per protocol which will be performed as soon as possible upon request, however, it should not delay treatment start with tocilizumab. Delay within ≤72 h from the time of reference due to preparing (cleansing) for colonoscopy or other investigations is up to investigator
- Clarification in the study flowchart that assessments Day 3 and 8 only are required after first administration of tocilizumab as well as the control visit at the Department of Rheumatology or Gastroenterology are to be performed approximately 4 weeks after first administration of tocilizumab
- Correction regarding immunohistochemically staining to rule out CMV infection which will be performed in the biopsies
- Based on regional guidelines for rheumatological patients the tocilizumab infusion over 30 minutes is allowed after 5. Cycle in the absence of infusion related events |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
